Abstract:
:In this study, 3D-pharmacophore models of Aurora B kinase inhibitors have been developed by using HipHop and HypoGen modules in Catalyst software package. The best pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9911), consists of one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic aliphatic moiety and one ring aromatic feature. Hypo1 was validated by test set and cross-validation methods. And the specificity of Hypo1 to Aurora B inhibitors was examined with the use of selective inhibitors against Aurora B and its paralogue Aurora A. The results clearly indicate that Hypo1 can differentiate selective inhibitors of Aurora B from those of Aurora A, and the ring aromatic feature likely plays some important roles for the specificity of Hypo1. Then Hypo1 was used as a 3D query to screen several databases including Specs, NCI, Maybridge and Chinese Nature Product Database (CNPD) for identifying new inhibitors of Aurora B. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five and docking studies to refine the retrieved hits, and some compounds selected from the top ranked hits have been suggested for further experimental assay studies.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Wang HY,Li LL,Cao ZX,Luo SD,Wei YQ,Yang SYdoi
10.1111/j.1747-0285.2008.00751.xsubject
Has Abstractpub_date
2009-01-01 00:00:00pages
115-26issue
1eissn
1747-0277issn
1747-0285pii
JPP751journal_volume
73pub_type
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